Ischemia, or the restriction of blood supply to tissue, may result in tissue damage in a process known as ischemic cascade, including shortage of metabolic requirements (i.e., oxygen and glucose), build-up of metabolic waste products, inability to maintain cell membranes, mitochondrial damage, and eventual leakage of autolyzing proteolytic enzymes into the cell and surrounding tissues. Brain ischemia may be chronic, e.g., leading to vascular dementia, or acute, e.g., causing a stroke. A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain caused by a clot or hemorrhage in a blood vessel. A clot may consist of at least one of a thrombus, embolus, or thromboembolus. A stroke in which a vessel is restricted or occluded by a clot is an ischemic stroke.
Ischemic stroke is the fourth leading cause of death in the United States, affecting over 795,000 patients per year and costing tens of billions of healthcare dollars. See, e.g., Veronique L. Roger et al., “Heart Disease and Stroke Statistics—2012 Update: A Report from the American Heart Association,” 125 Circulation e2-e220 (2012). Furthermore, patients who survive an ischemic stroke often require rehabilitation and management of symptoms including loss of brain function, motor skills, and memory. The extent of infarction (i.e., destruction of brain tissue) correlates with the extent of these lingering effects of the stroke and the mortality rate.
Of the existing treatment options for ischemic stroke, an older method, but still the primary method used in the United States, is to treat the clot with a clot-dissolving enzyme known as tissue plasminogen activator (hereinafter “tPA”). The use of tPA has two primary drawbacks. First, tPA has limited effectiveness, both in dissolving clots and providing overall benefits for the patients. Many patients do not qualify for tPA treatment because they do not arrive at the hospital within the effective time window of approximately 4.5 hours after the onset of stroke. Even when used within that window, tPA achieves only a limited decrease in the overall mortality rate. Second, tPA may present adverse effects, such as serious internal bleeding. See, e.g., Götz Thomalla et al., “Two Tales: Hemorrhagic Transformation But Not Parenchymal Hemorrhage After Thrombolysis Is Related to Severity and Duration of Ischemia: MRI Study of Acute Stroke Patients Treated with Intravenous Tissue Plasminogen Activator Within 6 Hours,” 38(2) Stroke 313-18 (2007).
A newer method of treating ischemic stroke is mechanical thrombectomy, in which a device physically engages with a clot and is used to drag the clot out of the body. Usually, an operator, e.g., a surgeon, first establishes a path for the thrombectomy device to reach a clot in the cerebral vasculature by inserting an initial guidewire (or guiding catheter) into an artery in a lower region of the body, such as the femoral artery. Then, the operator steers the guidewire through the arteries leading up to the brain and just past (i.e., distal to) the position of the clot. Favoring whichever path poses least resistance, the guidewire passes either between the clot and the blood vessel wall or through the clot. The operator inserts a microcatheter over the initial guidewire to follow its path until reaching a position distal to the clot. The initial guidewire may be removed and replaced with a new guidewire (hereinafter “pushwire” to differentiate from an initial guidewire). This pushwire has a thrombectomy device attached to its distal end to engage with the clot.
Currently, the most successful class of thrombectomy devices is based on neurovascular stent technology. Like stents, which are self-expandable and generally cylindrical, these devices tend to expand to the shape of the blood vessel walls. Thombectomy devices may comprise thin metal struts arranged to create a cell pattern. During device expansion, a clot may become enmeshed in the cells and compressed against a blood vessel wall. At this point, blood flow may be partially or fully restored in the vessel, thus relieving ischemia.
Unfortunately, abrupt restoration of blood supply to ischemic tissues may cause reperfusion injury, which is additional damage to blood vessels, potentially greater damage than even the ischemia. For example, reperfusion results in a sudden increase in oxygen in the tissues, causing a greater production of free radicals and reactive oxygen species that damage cells. The restored blood flow also brings more calcium ions to the tissues causing calcium overloading that may result in potentially fatal cardiac arrhythmias and accelerated cellular self-destruction. Furthermore, reperfusion may exaggerate the inflammation response of damaged tissue, triggering white blood cells to destroy damaged cells that may otherwise still be viable.
Reperfusion injury is highly significant and can visibly increase the infarct size (i.e., destroyed tissue) by as much as 30%. See, e.g., Andrew Tsang et al., “Myocardial Postconditioning: Reperfusion Injury Revisited,” 289(1) Am. J. Physiol. Heart & Circ. Physiol. H2-7 (2005); Heng Zhao et al., “Interrupting Reperfusion as a Stroke Therapy: Ischemic Postconditioning Reduces Infarct Size After Focal Ischemia in Rats,” 26(9) J. Cereb. Blood Flow & Metab. 1114-21 (2006); Giuseppe Pignataro et al., “In Vivo and In Vitro Characterization of a Novel Neuroprotective Strategy for Stroke: Ischemic Postconditioning,” 28(2) J Cereb. Blood Flow & Metab. 232-41 (2008).
Existing thrombectomy devices and/or systems do not systematically or even adequately control the restoration of blood flow so as to minimize and/or prevent reperfusion injury. Thus far, the prevention of reperfusion injury has been limited to the field of interventional cardiology. During the management of an ischemic event in the heart, a cardiologist will treat the blockade of a vessel with stents and/or balloon angioplasty to restore blood flow. Following reperfusion, a cardiologist uses an inflatable balloon to block and unblock blood flow through the vessel in intervals, thus modulating the resumed blood flow and minimizing reperfusion injury in a process called postconditioning.
Existing postconditioning devices and/or systems are designed for the large arteries of the heart (e.g., catheters with high longitudinal rigidity and large diameters); however, the narrow and tortuous arteries of the cerebral vasculature render these existing devices and/or systems inadequate or at least less desirable in the context of ischemic stroke.
Existing postconditioning devices and/or systems also fail to incorporate simultaneous clot capture. In order to initiate reperfusion and perform postconditioning simultaneously, both a reperfusion member and flow modulation member must be disposed concurrently in the same region. Particularly in the brain, where space constraints make it difficult to fit both an engaged reperfusion member and an active flow modulation member, no existing postconditioning devices and/or systems are designed to simultaneously deploy a clot capture member for reperfusion and perform postconditioning for the ischemic tissue.
Thus, there remains a need for postconditioning devices, systems and methods designed to prevent, minimize, and/or treat ischemic stroke and/or reperfusion injury by restoring and modulating blood flow in the cerebral vasculature.
Meanwhile, in addition to overlooking reperfusion injury, existing thrombectomy devices and/or systems are not designed to consistently bind with, capture, and/or retrieve clots. In fact, only about 30% of clots are successfully retrieved on a first pass (i.e., a deployment of the thrombectomy device). After five passes, 10% of clots still remain lodged. Furthermore, in 10% of cases, reperfusion is not even achieved while a thrombectomy device and/or system is engaged with the clot. Thus, there also remains a need for thrombectomy devices and/or systems that not only increase binding with clots but also increase reperfusion by creating a greater gap within the clot or between the clot and the blood vessel wall.